Performance of a Multianalyte 'Rule-Out' Assay in Pregnant Individuals With Suspected Preeclampsia

Abstract

Background: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia.

Methods: Prospective, multicenter cohort study of pregnant individuals presenting between 28^0/7 and 36^6/7 weeks' with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model.

Results: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%-33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P<0.0001; adjusted hazard ratio of 4.81 [3.69-6.27, P<0.0001]). The performance metrics for the assay to rule-out preeclampsia within 7 days of enrollment showed a sensitivity 76.4% (67.5%-83.5%), negative predictive value 95.0% (92.8%-96.6%), and negative likelihood ratio 0.46 (0.32-0.65). Assay performance improved if delivery occurred <37 weeks and for individuals enrolled between 28 and 35 weeks.

Conclusions: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment.

Registration: The study was registered on Clinicaltrials.gov (Identifier NCT02780414).

Keywords: biomarkers; hypertension; preeclampsia.

Figure 1.

Study flow chart.

Figure 2.

Survival curves (with 95% confidence margin) plotting the proportion of individuals without preeclampsia diagnosis vs the time to develop preeclampsia (in days), by assay status (at risk red or negative blue). Those who did not develop preeclampsia were censored at delivery or if lost to follow-up.

Figure 3.

Receiver-operating characteristic curves (with 95% confidence margin) of the predictive probabilities of the models with only clinical covariates and the model including clinical covariates and the assay. AUC indicates area under the curve.